鉴定PAN细胞焦亡相关基因作为甲状腺癌的预后指标

Identification of PANoptosis-related genes as prognostic indicators of thyroid cancer.

作者信息

Xie Diya, Huang Liyong, Li Cheng, Wu Ruozhen, Zheng Zhigang, Liu Fengmin, Cheng Huayong

机构信息

Department of General Surgery, First General Hospital of Fuzhou Affiliated of Fujian Medical University, Fuzhou, Fujian Province, China.

Department of Gastrointestinal Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China.

出版信息

Heliyon. 2024 May 23;10(11):e31707. doi: 10.1016/j.heliyon.2024.e31707. eCollection 2024 Jun 15.

DOI:10.1016/j.heliyon.2024.e31707

PMID:38845990

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11153176/

Abstract

BACKGROUND

Thyroid cancer (THCA) has become a common malignancy in recent years, with the mortality rate steadily increasing. PANoptosis is a unique kind of programmed cell death (PCD), including pyroptosis, necroptosis, and apoptosis, and is involved in the proliferation and prognosis of numerous cancers. This paper demonstrated the connection between PANoptosis-related genes and THCA based on the analyses of Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, which have not been evaluated yet.

METHODS

We identified PANoptosis-related differentially expressed genes (PRDEGs) by multi-analyzing the TCGA-THCA and GEO datasets. To identify the significant PRDEGs, a prognostic model was constructed using least absolute shrinkage and selection operator regression (LASSO). The predictive values of the significant PRDEGs for THCA outcomes were determined using Cox regression analysis and nomograms. Gene enrichment analyses were performed. Finally, immunohistochemistry was carried out using the human protein atlas.

RESULTS

A LASSO regression model based on nine PRDEGs was constructed, and the prognostic value of key PRDEGs was explored via risk score. Univariate and multivariate Cox regression were implemented to identify further three significant PRDEGs closely related to distant metastasis, lymph node metastasis, and tumor stage. Then, a nomogram was constructed, which presented high predictive accuracy for 5 years survival of THCA patients. Gene enrichment analyses in THCA were strongly associated with PCD pathways. CASP6 presented significantly differential expression during clinical T stage, N stage, and PFI events (P < 0.05 for all) and demonstrated the highest degree of diagnostic efficacy in PRDEGs (HR: 2.060, 95 % CI: 1.170-3.628, P < 0.05). Immunohistochemistry showed CASP6 was more abundant in THCA tumor tissue.

CONCLUSION

A potential prognostic role for PRDEGs in THCA was identified, providing a new direction for treatment. CASP6 may be a potential therapeutic target and a novel prognostic biomarker for THCA.

摘要

背景

甲状腺癌（THCA）近年来已成为一种常见的恶性肿瘤，死亡率呈稳步上升趋势。泛凋亡是一种独特的程序性细胞死亡（PCD），包括焦亡、坏死性凋亡和凋亡，并且参与多种癌症的增殖和预后。本文基于对基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据库的分析，论证了泛凋亡相关基因与甲状腺癌之间的联系，而此前尚未对这两个数据库进行过此类评估。

方法

我们通过对TCGA-THCA和GEO数据集进行多方面分析，确定了泛凋亡相关差异表达基因（PRDEGs）。为了识别显著的PRDEGs，使用最小绝对收缩和选择算子回归（LASSO）构建了一个预后模型。使用Cox回归分析和列线图确定显著PRDEGs对THCA预后的预测价值。进行了基因富集分析。最后，利用人类蛋白质图谱进行了免疫组织化学检测。

结果

构建了基于9个PRDEGs的LASSO回归模型，并通过风险评分探讨了关键PRDEGs的预后价值。实施单因素和多因素Cox回归以进一步确定与远处转移、淋巴结转移和肿瘤分期密切相关的另外3个显著PRDEGs。然后，构建了一个列线图，该列线图对THCA患者的5年生存率具有较高的预测准确性。THCA中的基因富集分析与PCD途径密切相关。CASP6在临床T分期、N分期和无进展生存期（PFI）事件中呈现出显著差异表达（所有P均<0.05），并且在PRDEGs中显示出最高的诊断效能（HR：2.060，95%CI：1.170 - 3.628，P<0.05）。免疫组织化学显示CASP6在THCA肿瘤组织中更为丰富。